Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme containing heme, which is the only rate-limiting enzyme outside the liver that can catalyze tryptophan metabolism to produce a series of metabolites including quinoline acid along kynurenine pathway (MacKenzie et al. Current Drug Metabolism, 2007, 8:237-244). Since 1990s, the important roles that played by indoleamine 2, 3-dioxygenase and the kynurenine pathway (KP) by which it catalyzes the tryptophan metabolism in a variety of disease processes has attracted increasing attentions.
Indoleamine 2,3-dioxygenase IDO catalyzes the oxidation reaction in which the essential amino acids—amino acids are converted into N-formyl-kynurenine by dioxygen, and is responsible for cleaning up the tryptophan in the human body. IDO causes tryptophan lacking in vivo microenvironment by degrading tryptophan, and then leads to the occurrence of diseases closely related to the lack of tryptophan such as cancer, cataracts, and nerve disorders. Therefore, searching of efficient IDO target-based inhibitor has become a hot topic in medicinal development in recent years.
Tryptanthrin is a quinoline indole alkaloids, of which the chemical name is indole [2,1-b] quinazoline-6,12-dione, and it is a yellow needle crystal which mainly exists in the Baphicacanthus cusia, Polygonum tinctorium, Isatis tinctoria and other Indigo producing plants. Meanwhile, tryptanthrin can also be extracted from the microorganism fermentation broth. In recent years, domestic and foreign scholars have partially researched the pharmacology of tryptophan, of which the effects mainly show in anti-bacterial, anti-inflammatory, anti-tumor and anti-parasitic aspects, etc. It has been shown that tryptanthrin is a very scarce medicinal resource with good potentials in research and development for new drugs. However, the development of tryptanthrin compounds is insufficient, and there is still a need in the art to further develop highly effective tryptanthrin derivatives of novel structure.